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Mechanism of Action: Two Completely Different Pathways Kisspeptin: The Hormonal Route Kisspeptin activates the reproductive hormone axis from the very top: Kisspeptin binds KISS1R on GnRH neurons in the hypothalamus GnRH is released into the portal circulation Pituitary releases LH and FSH Gonads respond testosterone production in testes, follicular development/ovulation in ovaries Limbic modulation kisspeptin also directly enhances activity in brain regions involved in sexual arousal (amygdala, cingulate cortex) via KISS1R expression in limbic structures Kisspeptin's sexual effects are therefore dual : hormonal (more testosterone/estrogen) AND neural (direct limbic activation)